hMGF's downfall and the introduction of PEGylated MGF
07-09-2006 01:40 AM
hMGF's downfall and the introduction of PEGylated MGF
I know a lot of you out there are really confused on everything that is going on with these peptides and I can assure you it tends to hit me pretty hard too when I begin researching them, unfortunately, IBE and I are absolutely obsessed with peptides to the point we will probably both join the same peptide rehab group soon haha.
I wanted to talk a little bit about why I feel the current version of MGF isn't really working and the use of a PEG molecule to fix the problem.
MGF, as it is being currently sold, is getting a bad rep from people due to the fact they feel that they are not seeing gains from it. Many people believe that the use of MGF in their cycles or protocols just flat out won't work, however, this is far from the truth. It isn't that MGF isn't working but, instead, because the molecule isn't able to survive long enough to exhibit its effects in the body. As some of you PubMed junkies know there aren't a lot of studies on Mechano Growth Factor (I say this because there are other types of MGF's) and there is only one of which that I have found that talks about its half life. The half life of MGF is said to be shorter than that of hIGF-1, which in multiple studies has been said to be ~20 minutes. Your body's biochemical solution to this is the introduction of IGFBP's or IGF Binding Proteins, which bind to IGF-1 and render it inactive, all the while preserving its half life as well; when the body is in need of more IGF-1, the levels of IGFBP's falls and plasma levels of IGF-1 once again increases. MGF, on the other hand, does not bind the IGFBP's despite MGF being a spliced variant of IGF-1. In one study conducted by Goldspink, he refers to a type of protein that does keep the half life of MGF extended. He more or less uses deductive reasoning to say that this is the only other thing that is left that could bind to MGF and MGF has to have something to keep it from being degraded after < 20 min., therefore, we propose it is this. Since our bodies do not product an amount of MGF similar to that at which we inject, it is hard to say what happens to the MGF once we inject dosages such as 100mcg x 2 bilaterally. If the half life is roughly 10 minutes, it would be absolutely impossible for the mechanism by which MGF acts through to cause rapid proliferation, since the MGF would quickly saturate the area it was injected and deplete its resource pathway, and it also seems improbable for the body to have enough proteins to keep the MGF from degrading, since it is not used to the large influx of exogenous MGF.
Now that we have talked about the problem of MGF's half life (we will touch on how to fix this problem later), lets begin to talk about another aspect of MGF's eventual demise: packaging/shipping/storage. One of the biggest misconceptions people seem to have is that LR3 IGF-1 and MGF are very similar and, therefore, would act similar in solution and in the body. This is about as far from the truth as it gets. If you think to substances such as L-Carnitine compared to Acetyl-L-Carnitine you can see the vast difference a small addition can make to a molecule. An acetyl group is merely a CH3 group attached to a carbon that is double bonded to an oxygen, not much of a difference, especially when very large proteins (with 50+ carbons already attached) but the effects can be largely different. LR3 IGF-1 was designed by GroPep International, a company who marketed the product for scientific and possible pharmaceutical use. They created a protein sequence that prevented rapid enzymatic degredation (destruction of the molecule by the body), which increased the half life. MGF does not have any such addition. MGF does act a lot like IGF-1Ea, however, IGF-1Ea is vastly different than LR3 IGF-1 in the way it acts in the bloodstream. MGF is actually water soluble, unlike LR3 IGF-1, and again unlike LR3 IGF-1 it is very unstable in solution. According to Sigma and Phoenix Peptides, MGF MUST be kept below freezing to prevent peptide degradation, once you go above a certain point you will severely limit the mass of active peptide that you receive. Once reconstituted MGF must be kept as close to freezing as possible, since water freezes at 0*C and it is water soluble it must be kept above 0*C. At this temperature it is suggested that the peptide will last ~1 week. Phoenix has stated that, although no studies have been done on MGF once reconstituted, they recommend refreezing it at -70*C. I don't know about you but I don't have access to liquid nitrogen so that I can refrigerate something to those levels! Not only that but this process can only be done once as repetitive freezing/thawing can cause further peptide degredation. Reconstituted MGF will last ~3-6 months when refrigerated at -70*C. Phoenix has also stated that shaking of the bottle or even constant vibrations (which can be caused by loud bass as well) will also degrade the peptide, but it is mostly stable (for only on week) if kept near freezing based on structure.
So lets assume for moment that someone who has synthesized your MGF, walked it to you as slowly as possible without shaking it or disturbing it in any way, kept it below freezing the entire time, reconstituted it and kept it at 0.1*C in a pitch black refrigerator, you would still only have 1 week to use it all up! Do you really feel that a peptide, which is NOT a hormone, can really give you results this quickly? Definitely not. It is almost impossible that the peptide is shipped by the company who created it to the person who ordered it and it is kept completely dry and below freezing (often coming from China), and therefore once again some peptide degredation as occurred. Then when shipping to you, again it is near impossible to keep the temperature cold enough to prevent degredation and your mass% of MGF is continuing to fall.
Now after all this pessimistic talk what can be done? MGF has a couple different forms, one of which is a d-arg substituted version. Some forms of MGF are more stable than others and still have their functional group intact and work in the same manner. Instead of altering the MGF protein sequence, however, it is better to use something called pegylation. Pegylation uses a substance called polyethylene glycol, which can be attached to a protein molecule and create a "shield" around the protein itself to prevent things such as enzymatic degredation and rapid glomerular excretion while decreasing immunogenicity (the rate at which the substance causes an immune response) and increasing overall half life. This is achieved through the unique structure of ethylene glycol. It creates a steric hindrance (which is basically a large negatively charged shield that pushes away other negatively charged particles, much in the same way two negatively charged magnets repel each other when you push them together) around the protein or peptide and protects clevage points (which are poitns at which the enzyme can attack the peptide and break it in half so to speak) while NOT blocking the are where the peptide/protein attaches to the receptor. Think of it as a raincoat that protects you from the rain but still has small holes for your hands, feet, and face. Depending on the size of the molecule, depends on what size PEG molecule you want to use. PEG weights vary greatly. Too large of a PEG and you can actually block the receptor binding site. However, if the right weight is chosen, it can have profound effects on protein/peptide stability and a reduction in toxicity. Even if the peptide/protein itself is not water soluble, many times the addition of PEG will create a water soluble compound.
The half life of a PEG molecule can be enhanced greatly. Instead of the < 20 minute half life of regular MGF, pegylated MGF can have a half life of many days, although the exact half life is not know. This has brought scientists such as Yang and Goldspink, who lead their field in IGF-1 Axis research, to use pegylated MGF in their studies as opposed to regular MGF to increase experimental accuracy with the extended stability and half life. This would allow someone to inject PEG MGF twice or possibly once per week while not having to worry about peptide degredation in solution as PEG molecules repel away from themselves as well. The only difference now, is that instead of a localized MGF, we have the possibility of a systemic MGF, which COULD be detrimental, but it is yet to be seen as we have not yet tested this theory. At the correct dosage it could work out VERY VERY well as it would allow total body proliferation, but if taken in too high dosages, could inhibit differentiation.
Bottom line, dump the current MGF versions, biopharmaceuticals are the way of the future and PEG structures have shown VERY significant results in current pharmaceutical drugs. I see PEG MGF being a great supplement and we should look more to these longer lasting peptides/proteins such as LR3 IGF-1, MGF, and many others to come!
Last edited by LakeMountD; 07-09-2006 at 09:52 AM.
07-09-2006 01:44 AM
Damn, you said talk a little bit. LIAR!!!!!
I look forward to reading this, but not at 2am
07-09-2006 01:46 AM
My hands hurt
Originally Posted by Beowulf
07-09-2006 01:53 AM
my brain hurts from all those big words...like molecule and research...
07-09-2006 02:01 AM
07-09-2006 08:30 AM
Good post Lake
07-09-2006 10:46 AM
Lake..........i love you.
good work bro.
07-09-2006 11:00 AM
Great information, Lake and well written.
07-09-2006 11:19 AM
07-10-2006 01:18 AM
The only thing I got out of this whole article was "ethylene".
Finally - something I know something about!!!
Now - can we start talking about reflux ratio's, tray spacing, tray types, reboilers, and cryogenic distillation??????
07-10-2006 09:37 AM
Haha damn ChE's.
Originally Posted by jmh80
And yes we can talk about them:
Reflux Ratio: The pain to tolerance ratio of heartburn
Tray Spacing: The space between two adjacent food trays on the table in basic training
Tray Types: Air Force, Marine, Army, or Navy tray type (depending on which basic training)
Cryogenic Distillation: Superman's method of bathing
Basically the article I wrote was to inform people across various other boards as well. The topic has been coming up a lot lately and I feel people needed to know the truth and see the future of technology when it comes to peptides.
07-11-2006 12:12 PM
I finally got the chance to read carefully. Great post, Lake. MGF seems to have so much potential; it is great to see there is a plan in place. I've seen MGF on some lists, and it is definitely not pegylated.
07-11-2006 12:28 PM
I can assure you that at first there will only be ONE company that will have it . We can't source though as you know so I can't say.
Originally Posted by Beowulf
07-21-2006 12:36 AM
Incredible post. You have laid out a credible hypotheses and have presented evidence and reasoning to support it.
Does PEG MGF have the potential to be administered via the cell mediation technology?
Last edited by bkshilo; 07-21-2006 at 12:46 AM.
Reason: Mis-spelling; choice of words
07-21-2006 12:51 AM
Nice info lake, so the current mgf is not good beyond 20 mins of adding solution? sorry im simple.
07-21-2006 09:56 AM
bkshilo: If by cell mediated technology you are referring to a viral mediated substance I am not sure. I don't believe it would work via a "true" viral mediated substance since viruses use RNA transcription to force the cells to create the sequence they inject.
somehwhatgifted: No it doesn't mean it will only last 20 minutes once reconstituted, it means that the half life (once injected) is less than 20 minutes in your body. The reconstituted formula lasts 1-2 weeks. It is not known whether it is 1 or 2 but some pharmacologists have told me that based on structure, it will probably last closer to 1 week once reconstituted and that is even being refrigerated at 0-5*C.
Thanks for the kind words guys.
07-21-2006 02:26 PM
Well, your response demonstrates your extensive knowlege and expertise, and I am already left in the dust!
A supplement comany, IBE, has a forum on this board and some of their supplements supply peptides thru oral administration by a mechanism that is described as "Cell-Mediated Technology". Examples: Oratropin, Hexatropin, Ectotropin
So my question is: could PEG MGF be administered orally thru this "Cell-Mediated Technology" mechanism? I'm a fairly ignorant layperson when in comes to how all this stuff works.
NOTE TO MODS: My understanding is that IBE's existing supplement line, and the underlying delivery technology, can be discussed. Please edit if my understanding is incorrect.
07-21-2006 02:35 PM
There would be no reason to use cell mediated technology since usually the reason for that is to extend bioavailability and half life of the product, however, in this case it is being accomplished through the PEGylation process.
Originally Posted by bkshilo
07-28-2006 05:56 PM
Well guys I received my PEG-MGF today. I just wanted to let you guys know how I will be testing it.
We don't know the true half-life of it as there isn't any research on it for the most part, but we speculate it to be around 4-8 days.
With that being said and also with the fact that we know high doses of MGF in muscles that have been worked a while ago can actually inhibit differentiation. Therefore it would seem the best way to dose this compound is 2x per week with loser doses. We aren't positive but I feel that this will go somewhat systemic and therefore doses should be kept much lower, but it isn't positive. I will find out soon enough. It is now in stock but I am not allowed to give sources so you will have to figure everything out on your own .
07-28-2006 06:24 PM
4-8 days. That's way longer then the hMGF.
What are "lower" doses compared too? IGF? Is that 2x per week in the whole body or just that site?
I was planing to do a total of 150mcg per muscle group once a week. Should I cut this back to 50mcg?
Thanks. Your info is most defenitly invaluable.
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